This invention relates to electrophoresis and to capillary electrophoresis used in conjunction with electrospray ionization mass spectrometry.
Electrophoresis is fundamentally the movement of charged particles within an applied electric field. Capillary electrophoresis (CE) is a known process. In capillary electrophoresis, a sample is injected at one end of the capillary. A detector is attached on the capillary at the other end of the capillary distant from the sample. A voltage is applied along the length of the capillary.
With the electric potential applied, two separate flow effects occur. The first of these flow effects is a gross sample flow effect. The sample moves as a mass into the capillary. The second of these flow effects is the electrophoretic flow. This causes the constituents of the sample having differing electric charges to move relative to the main stream of fluid within the capillary. The portions of the sample having differing electric charges are thereby separated in the capillary.
Different detectors may be used to analyze the sample after the separation has occurred. In a system that combines capillary electrophoresis with electrospray ionization (ESI) and mass spectrometry (MS), the output of the capillary is input to an electrospray assembly. The electrospray ionization is accomplished by placing a high voltage potential at the outlet of the separation capillary with respect to the capillary inlet to the mass spectrometer. The separation capillary also requires a high voltage potential placed between its inlet and outlet. The separated portions of the sample are dispersed by the electrospray into a fine aerosol as they exit the capillary. The droplets of the aerosol are then observed by mass spectrometry.
Capillary electrophoresis coupled with electrospray ionization and mass spectrometry is a relatively difficult procedure. The capillary must be mechanically connected to the rest of the system and positioned with respect to a detector. The capillaries are small and fragile, and the alignment process with the electrospray ionization assembly into the mass spectrometer may be difficult, time consuming, and may damage the capillary.
The system is further complicated by a variety of factors, such as the need to cool the capillary. This cooling is required because the small capillary is subject to electrical resistance heating during the period of time electrophoresis potential voltage is applied. A small current under high voltage flowing in the capillary generates heat. The cooling is required to prevent damage to the capillary and to prevent variations in temperature during analysis of the sample from impacting the results of the analysis. Excess heat may cause diffusion of the separated portions of the sample that migrate through the capillary at different speeds. The heat and its resultant diffusion degrade separation and following classification result that is the purpose of using electrophoresis.
An additional complication is that capillary electrophoresis systems and ESI-MS systems are structured as two separate systems that must be configured together to perform a CE ESI-MS measurement. Different interfaces and standard connections between different types and brands of instruments cause interconnection issues that also may create a safety hazard for users if the connections are not set properly, especially given the high voltages involved in both systems.
There is therefore a need for improved CE ESI-MS systems that improve functionality and interconnection systems between CE and ESI-MS systems. There is a need for a CE system comprising an error detection circuit suitable for individually interfacing with two or more types of electrospray ionization-mass spectrometers.